Clinical question: Does diltiazem increase the risk of major bleeding in patients on apixaban or rivaroxaban?
Background: Diltiazem is a potent CYP3A4 inhibitor and a mild P-glycoprotein inhibitor. Previous studies have shown that co-administration with diltiazem increases the bleeding risk and plasma levels of apixaban and rivaroxaban.
Study design: Retrospective cohort study with propensity score matching
Setting: Medicare database for patients aged 65 and older in the U.S.
Synopsis: This study included 205,155 Medicare beneficiaries aged 65 and older with atrial fibrillation newly prescribed apixaban or rivaroxaban along with diltiazem or metoprolol. During a median follow-up of 120 days, patients on diltiazem had a higher risk of major bleeding compared to those on metoprolol (hazard ratio,1.21; number needed to harm, 99) and an increased risk of death from major bleeding (hazard ratio, 1.22). The risk was dose-dependent, with doses >120 mg/day linked to even higher risks. The study did not analyze the effects of reducing apixaban/rivaroxaban doses with diltiazem, so such adjustments cannot be recommended without further evidence.
Bottom line: Diltiazem is associated with an increased bleeding risk when combined with apixaban or rivaroxaban. Clinicians should consider alternatives and involve patients in shared decision-making regarding rate control options before prescribing diltiazem.
Citation: Ray WA, et al. Serious bleeding in patients with atrial fibrillation using diltiazem with apixaban or rivaroxaban. JAMA. 2024;331(18):1565-75. doi:10.1001/jama.2024.3867
Dr. Purushothaman is an academic hospitalist in the section of hospital medicine at UPMC Presbyterian Hospital, and a clinical assistant professor of medicine at the University of Pittsburgh School of Medicine, both in Pittsburgh.